Gene expression of transferrin and transferrin receptor in brains of control vs. iron-deficient rats

The mechanism of the regulation of transferrin (Tf) and transferrin receptor (TfR) levels in rat brain by dietary iron status is not fully elucidated. We examined Tf and TfR protein and mRNA contents in various brain regions affected by dietary iron deficiency, and analyzed the relationships between protein and mRNA contents in brains of control vs. iron-deficient rats. In a region-specific fashion, iron-deficient diet decreased significantly brain iron concentration by 22-63%, and increased Tf level by 22-130% and TfR level by 74% in thalamus and 40% in cortex. Tf mRNA content decreased by 20-50% in most brain regions demonstrating inverse correlation of Tf and its mRNA in response to iron deficiency. TfR mRNA levels remained unaffected by iron status. The corpus callosum, white matter of the cerebellum and lateral ventricles expressed highest levels of Tf mRNA, whereas TfR mRNA levels was lowest in these regions, but highest in cortex, hippocampus, and the gray matter of the cerebellum. The data demonstrate that the cells in brain have the capacity to maintain minimum iron levels during iron deficiency. This capacity may be associated with increased iron-Tf uptake from plasma, stabilization of TfR mRNA, or increased Tf mRNA translation efficiency in specific cell types within the brain.